Spatial and age-related changes in the microstructure of dystrophic and healthy diaphragms.
Duchenne muscular dystrophy (DMD) is a progressive degenerative disease that results in fibrosis and atrophy of muscles. The main cause of death associated with DMD is failure of the diaphragm. The diaphragm is a dome-shaped muscle with a fiber microstructure that differs across regions of the muscl...
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0183853&type=printable |
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| author | Catherine C Henry Kyle S Martin Bridget B Ward Geoffrey G Handsfield Shayn M Peirce Silvia S Blemker |
| author_facet | Catherine C Henry Kyle S Martin Bridget B Ward Geoffrey G Handsfield Shayn M Peirce Silvia S Blemker |
| author_sort | Catherine C Henry |
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| description | Duchenne muscular dystrophy (DMD) is a progressive degenerative disease that results in fibrosis and atrophy of muscles. The main cause of death associated with DMD is failure of the diaphragm. The diaphragm is a dome-shaped muscle with a fiber microstructure that differs across regions of the muscle. However, no studies to our knowledge have examined spatial variations of muscle fibers in dystrophic diaphragm or how aging affects those variations in DMD. In this study, diaphragms were obtained from mdx and healthy mice at ages three, seven, and ten months in the dorsal, midcostal, and ventral regions. Through immunostaining and confocal imaging, we quantified sarcomere length, interstitial space between fibers, fiber branching, fiber cross sectional area (CSA), and fiber regeneration measured by centrally located nuclei. Because DMD is associated with chronic inflammation, we also investigated the number of macrophages in diaphragm muscle cross-sections. We saw regional differences in the number of regenerating fibers and macrophages during the progression of DMD in the mdx diaphragm. Additionally, the number of regenerating fibers increased with age, while CSA and the number of branching fibers decreased. Dystrophic diaphragms had shorter sarcomere lengths than age-matched controls. Our results suggest that the dystrophic diaphragm in the mdx mouse is structurally heterogeneous and remodels non-uniformly over time. Understanding regional changes in dystrophic diaphragms over time will facilitate the development of targeted therapies to prevent or minimize respiratory failure in DMD patients. |
| format | Article |
| id | doaj-art-df96e367d22e4bddb56279640e273edb |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-df96e367d22e4bddb56279640e273edb2025-08-20T02:03:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018385310.1371/journal.pone.0183853Spatial and age-related changes in the microstructure of dystrophic and healthy diaphragms.Catherine C HenryKyle S MartinBridget B WardGeoffrey G HandsfieldShayn M PeirceSilvia S BlemkerDuchenne muscular dystrophy (DMD) is a progressive degenerative disease that results in fibrosis and atrophy of muscles. The main cause of death associated with DMD is failure of the diaphragm. The diaphragm is a dome-shaped muscle with a fiber microstructure that differs across regions of the muscle. However, no studies to our knowledge have examined spatial variations of muscle fibers in dystrophic diaphragm or how aging affects those variations in DMD. In this study, diaphragms were obtained from mdx and healthy mice at ages three, seven, and ten months in the dorsal, midcostal, and ventral regions. Through immunostaining and confocal imaging, we quantified sarcomere length, interstitial space between fibers, fiber branching, fiber cross sectional area (CSA), and fiber regeneration measured by centrally located nuclei. Because DMD is associated with chronic inflammation, we also investigated the number of macrophages in diaphragm muscle cross-sections. We saw regional differences in the number of regenerating fibers and macrophages during the progression of DMD in the mdx diaphragm. Additionally, the number of regenerating fibers increased with age, while CSA and the number of branching fibers decreased. Dystrophic diaphragms had shorter sarcomere lengths than age-matched controls. Our results suggest that the dystrophic diaphragm in the mdx mouse is structurally heterogeneous and remodels non-uniformly over time. Understanding regional changes in dystrophic diaphragms over time will facilitate the development of targeted therapies to prevent or minimize respiratory failure in DMD patients.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0183853&type=printable |
| spellingShingle | Catherine C Henry Kyle S Martin Bridget B Ward Geoffrey G Handsfield Shayn M Peirce Silvia S Blemker Spatial and age-related changes in the microstructure of dystrophic and healthy diaphragms. PLoS ONE |
| title | Spatial and age-related changes in the microstructure of dystrophic and healthy diaphragms. |
| title_full | Spatial and age-related changes in the microstructure of dystrophic and healthy diaphragms. |
| title_fullStr | Spatial and age-related changes in the microstructure of dystrophic and healthy diaphragms. |
| title_full_unstemmed | Spatial and age-related changes in the microstructure of dystrophic and healthy diaphragms. |
| title_short | Spatial and age-related changes in the microstructure of dystrophic and healthy diaphragms. |
| title_sort | spatial and age related changes in the microstructure of dystrophic and healthy diaphragms |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0183853&type=printable |
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